Field of the Invention
The present disclosure is generally directed to compositions and methods for treating apicomplexan protozoan related disease, such as toxoplasmosis and cryptosporidiosis.
Description of Related Art
Toxoplasma gondii (T. gondii) and Cryptosporidium parvum (C. parvum) are apicomplexan parasites that cause serious diseases in humans (toxoplasmosis and cryptosporidiosis) with inadequate treatment options. C. parvum infection has been implicated in 15-20% of childhood diarrhea cases in developing countries and can lead to life-threatening illness in immunocompromised persons. The only approved medicine for C. parvum infection, nitazoxanide, is expensive and not very effective for treating immunocompromised patients. Toxoplasmosis also leads to life-threatening situations in immunocompromised patients. T. gondii infection of pregnant women can result in severe birth defects or miscarriage.
The calcium-dependent protein kinase-1 orthologs of both T. gondii (TgCDPK1) and C. parvum (CpCDPK1) have attracted interest as potential drug targets for these parasites. CDPK1 belongs to a family of serine/threonine protein kinases found in plants and Apicomplexa but not in humans or other animals. Recent genetic and chemical evidence suggests that TgCDPK1 plays critical role in the lifecycle of T. gondii parasites by controlling the exocytosis of micronemes, which are specialized organelles that contain a number of proteins involved in parasite invasion and egress. CpCDPK1 is likely of importance to the lifecycle of C. parvum for similar reasons.